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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Earlv expression of antiinsulin autoantibodies of humans and the NOD mouse: Evidence for early determination of subsequent diabetes
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Earlv expression of antiinsulin autoantibodies of humans and the NOD mouse: Evidence for early determination of subsequent diabetes

机译：人类和NOD小鼠抗胰岛素自身抗体的早期表达：早期确定随后的糖尿病的证据

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With the development of an insulin autoantibody (IAA) assay performed in 96-well filtration plates. we have evaluated prospec- tively the development of lAA in NOD mice (from 4 weeks of age) and children (from 7 to 10 months of age) at genetic risk for the development of type 1 diabetes. NOD mice had heterogeneous expression of lAA despite being inbred. lAA reached a peak between 8 and 16 weeks and then declined. lAA expression by NOD mice at 8 weeks of age was strongly associated with early devel- opment of diabetes, which occurred at 16--18 weeks of age (NOD mice lAA+ at 8 weeks: 83% (5/6) diabetic by 18 weeks versus 11 % (1/9) of IAA negative at 8 weeks; P < .01). In man. lAA was frequently present as early as 9 months of age. the first sampling time. Of five children found to have persistent lAA before 1 year of age, four have progressed to diabetes (all before 3.5 years of age) and the fifth is currently less than age 2. Of the 929 children not expressing persistent IAA before age 1, only one has pro- gressed to diabetes to date (age onset 3), and this child expressed IAA at his second visit (age 1 .1). In new onset patients, the highest levels of lAA correlated with an earlier age of diabetes onset. Our data suggest that the program for developing diabetes of NOD mice and humans is relatively "fixed" early in life and. for NOD mice, a high risk of early development of diabetes is offen deter- mined by 8 weeks of age. With such early determination of high risk of progression to diabetes, immunologic therapies in humans may need to be tested in children before the development of IAA for maximal efficacy.
机译：随着胰岛素自身抗体（IAA）分析技术的发展，在96孔滤板中进行了检测。我们分别评估了NOD小鼠（从4周龄开始）和儿童（从7至10个月大）患有1型糖尿病发生遗传风险的lAA的发展。尽管近交，NOD小鼠仍具有异型的lAA表达。 lAA在8到16周之间达到峰值，然后下降。 8周龄的NOD小鼠的lAA表达与糖尿病的早期发展密切相关，糖尿病的早期发展发生在16--18周龄（8周NOD小鼠lAA +：18周时有83％（5/6）糖尿病的人）与8周时IAA阴性的11％（1/9）相比； P <.01）。在男人。 lAA早在9个月大时就出现了。第一次采样时间。被发现在1岁之前患有持续性IAA的5名儿童中，有4名已发展为糖尿病（均在3.5岁之前），目前有5名年龄低于2岁。在929名1岁之前未表现出持续性IAA的儿童中，只有929名儿童迄今为止，一个人已经发展为糖尿病（发病年龄为3岁），这个孩子在第二次就诊时表现为IAA（1.1岁）。在新发病的患者中，最高的lAA水平与较早的糖尿病发病年龄有关。我们的数据表明，在NOD小鼠和人类中发展糖尿病的程序在生命早期和阶段相对“固定”。对于NOD小鼠，由8周龄决定了糖尿病早期发展的高风险。如此早期确定罹患糖尿病的高风险，可能需要在开发IAA之前在儿童中对人类的免疫疗法进行测试，以取得最大功效。

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